ABSTRACT AND SUMMARY Functional decline in patients with mild cognitive impairment (MCI) is an important issue in dementia research. MCI has been defined primarily as a cognitive syndrome;diagnostic criteria stipulate that little or no impairment in Instrumental Activities of Daily Living (IADLs) be present. Yet MCI is also a dynamic transitional state between cognitive aging and dementia in which IADL decline clearly occurs and drives clinical judgments of conversion to AD and other dementias. Delineating the course of functional change in MCI remains essential for characterizing this construct and for scientific and clinical differentiation of cognitive aging, MCI and AD. The existing R01 project (Functional Change in MCI) has systematically studied two key IADLs-- medical decision-making capacity (MDC) and financial capacity (FC). These are "real world" activities that depend on integration of multiple component abilities and due to their complexity are vulnerable to the early cognitive declines found in MCI. Study findings to date have provided substantial new information regarding the nature, extent and rate of functional decline in MCI. At baseline, patients with aMCI have significant deficits in MDC and FC relative to controls;initial measurable functional declines in FC and MDC occur over a 1 to 3 year period;following conversion to AD functional decline in MCI accelerates;and FC is a strong predictor of both clinical progression and conversion to AD. Cognitive modeling has revealed primary cognitive predictors of declining FC (written arithmetic) and MDC (verbal memory). Since our application in 2004, the topic of MCI has undergone extensive scientific study and diagnostic revision. In addition, there has been intense scientific interest in biomarkers and their potential to track disease progression. In particular, neuroimaging has emerged as a potential biomarker to identify patients with MCI progressing to AD. As a result, new and exciting opportunities for investigating functional change in MCI now exist. One promising area concerns investigating the neuroanatomical basis of IADL change in MCI and AD. The dementia field needs new models of IADL decline linked directly to brain that integrate neuroanatomical and associated cognitive change. A second area of opportunity concerns development of brief, performance based IADL measures sensitive to prodromal AD. For example, a brief performance measure of FC sensitive to prodromal AD would represent a valuable contribution to both clinical practice and clinical trial research. This R01 competing renewal application builds upon and extends the current project's studies of functional change in aMCI by pursuing three related aims: -Aim 1 (Neuroimaging): Longitudinally investigate whether volumetric changes in angular gyrus and medial frontal regions are associated with declining financial capacity in patients with MCI -Aim 2 (Translational): Develop and validate a brief, performance based measure of financial capacity sensitive to progression and conversion in prodromal AD -Aim 3 (Long Term Follow-Up): Conduct long-term follow-up of the existing study cohort to continue to investigate the sequence of functional task decline in patients with aMCI